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This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0151v1 42/6/479    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ikeda, K. Articles by Tajima, N. Search for Related Content PubMed PubMed Citation Articles by Ikeda, K. Articles by Tajima, N.

K Ikeda, Department of Pharmacology, Jikei University School of Medicine, Tokyo, 105-8461, Japan
K Tojo, Division of Endocrinology and Diabetes, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
Y Inada, Division of Endocrinology and Diabetes, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
Y Takada, Division of Endocrinology and Diabetes, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
M Sakamoto, Division of Endocrinology and Diabetes, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
M Lam, Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Oleans, United States
W Claycomb, Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, United States
N Tajima, Division of Endocrinology and Diabetes, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

Correspondence: Keiichi Ikeda, Email: ikedak{at}jikei.ac.jp

Abstract

Despite our knowledge on the regulation of urocortin (Ucn) I and its related peptides in the heart, the possible involvement of cardiovascular stress substances, such as cytokines or angiotensin II (Ang II), on this regulation remains to be fully elucidated. We therefore evaluated the potential role of cardiovascular stress substances on the regulation of the Ucn-corticotropin-releasing hormone (CRH) receptor system in HL-1 cardiomyocytes using a Ucn I-specific radioimmunoassay, conventional RT-PCR and quantitative real-time RT-PCR. Ucn I mRNA levels were shown to be up-regulated by LPS, TNF-, Ang II, H2O2, and pyrrolidinedithiocarbamate (PDTC). The LPS- and Ang II-induced increase in Ucn I mRNA levels was abolished by tempol. In addition, the secretion of Ucn I from HL-1 cardiomyocytes was stimulated by LPS and TNF-. On the contrary, Ucn II mRNA was increased by TNF- alone and Ang II with tempol. And the TNF--induced increase in Ucn II mRNA was abolished by erythromycin and PDTC. These results suggested that Ucn I mRNA may be up-regulated by oxidative stress, whereas Ucn II mRNA may be up-regulated by the activated nuclear factor-B, i.e., inflammatory stress. CRH-R2 mRNA may be negatively regulated by the increase in expression of Ucn I and/or Ucn II mRNA. In conclusion, the Ucn-CRH receptor system may be regulated by two major forms of cardiac stresses, i.e., oxidative and inflammatory stress, and may play a critical role in cardiac stress adaptation in heart diseases.